Zalsupindole
Zalsupindole, also known by its code names DLX-001 and AAZ-A-154 and as -5-methoxy-N,''N''-dimethyl-α-methylisotryptamine, is non-hallucinogenic serotonin receptor agonist and psychoplastogen of the isotryptamine family related to psychedelic tryptamines such as dimethyltryptamine. It is under development for the treatment of major depressive disorder and other central nervous system disorders. The drug is taken orally.
It acts as a partial agonist of the serotonin 5-HT2A receptor and also interacts with other serotonin receptors. The drug activates the serotonin 5-HT2A receptor with sufficiently high efficacy to promote neuroplasticity but not with adequate efficacy to cause psychedelic effects. It does not produce psychedelic-like effects in animals or humans but does produce antidepressant-like effects in animals.
Zalsupindole was first described in the scientific literature by 2021. It was developed by David E. Olson and colleagues at the University of California, Davis and Delix Therapeutics. As of January 2026, it is in phase 1 clinical trials and a phase 2 trial is being planned.
Use and effects
A phase 1 dose-ranging clinical trial found that zalsupindole is non-hallucinogenic in humans across a dose range of 2 to 360mg orally. Nonetheless, it produced changes in brain function as measured by quantitative electroencephalography.Side effects
s of zalsupindole include dose-dependent nausea, headache, and dizziness.Pharmacology
Pharmacodynamics
Zalsupindole is a non-selective serotonin receptor modulator including of the serotonin 5-HT2A receptor. It acts as a low-potency, low-efficacy partial agonist of the serotonin 5-HT2A receptor, with an of 8,200nM and an of 17%. The drug is also a moderate-efficacy partial agonist of the serotonin 5-HT2C receptor, with an of 3,300nM and an of 70%. Other activities have also been reported. It is selective for the serotonin 5-HT2 receptors over a number of other receptors, including the serotonin 5-HT1A receptor, dopamine receptors, adrenergic receptors, and the κ-opioid receptor, among others. The drug is a silent antagonist of the serotonin 5-HT2B receptor, with an of 27,600nM.Zalsupindole is orally bioavailable and centrally penetrant in animals. It is a psychoplastogen via activation of the serotonin 5-HT2A receptor and rapidly and persistently increases neuroplasticity in preclinical research. The serotonin 5-HT2A receptor antagonist ketanserin abolishes the psychoplastogenic effects of zalsupindole. Zalsupindole produces comparable psychoplastogenic effects to serotonergic psychedelics like psilocin and dimethyltryptamine as well as to the dissociative ketamine. Animal studies have found that the drug produces antidepressant-like effects without causing psychedelic-like effects such as the head-twitch response. It does not produce hyperlocomotion at therapeutically relevant doses. In accordance with its serotonin 5-HT2B receptor antagonism, zalsupindole showed no cardiovascular safety signals in animals.